The Bills finished tied with the Boston Patriots for the AFL's Eastern Division title in 1963, losing the playoff game to the Pats. They would win the division for the next three years, together with two American Football League championships, in 1964 and in 1965. McDole and his defensive linemates (left tackle Jim Dunaway, right tackle Tom Sestak, and right end Tom Day) held the opposition without a rushing touchdown in 17 straight games over the 1964–1965 seasons. McDole was the defensive team captain during those years, an AFL All-Star in 1965 and 1967. He was selected to the All-Time All-AFL second team.
From 1971 through 1978, McDole was a key defensive player at left defensive end for the NFL Washington Redskins, under head coach George Allen from 1971 to 1977, and, in his final year, under head coach Jack Pardee. By that time, he was quite slow, not a big threat as a pass-rusher, but very stout against the run, rarely out of position, and quick to seize opportunities for turnovers. In 1972, the Redskins won the NFC championship game of the 1972–73 NFL playoffs against the Dallas Cowboys, when they limited the Cowboys to 3 points, 96 rushing yards on 21 carries, and, despite Roger Staubach as their quarterback, to 73 net passing yards, as McDole held his own against the opposing right offensive tackle, Rayfield Wright, a member of the Pro Football Hall of Fame. However, though the defense allowed only 14 points, the team lost Super Bowl VII to the Miami Dolphins.